The validity of over-the-counter skin, hair, and nail recommendations for adult patients with cancer: A systematic review

Importance Patients undergoing cancer treatment experience a multitude of skin, hair, and nail adverse events, prompting them to use non-evidence-based and often restrictive over-the-counter (OTC) recommendations to alleviate their symptoms. Comprehensively assessing evidence-based OTC modalities is crucial to enable cancer patients to comfortably resume their lives post-treatment and integrate clinically sound practices into their self-care routines. Objective Perform a systematic review and assessment of evidence-based OTC skin, hair, and nail care recommendations for adult patients undergoing cancer treatment. Evidence review PubMed, Cochrane, Embase, and Medline databases were searched in March 2023 to identify English articles addressing OTC skin, hair, and nail care recommendations for adult patients before, during, and after cancer chemotherapy or radiation therapy (RT). Quality was assessed with Oxford Centre for Evidence Based Medicine criteria. Findings 2192 unique articles were screened, of which 77 met inclusion criteria consisting of 54 randomized controlled trials (RCT), 8 non-randomized controlled cohorts, 1 non-randomized controlled clinical trial, 3 controlled prospective cohorts, 4 prospective cohorts, 2 controlled clinical trials, 1 prospective comparative study, 2 case reports, and 2 case series discussing 9322 patients. An additional article outside of our database search was included for a total of 78 articles. OTC skin care treatments with the best quality of evidence included moisturizing creams. Our review revealed a paucity of evidence-based hair and nail care practices. Conclusions and relevance This systematic review serves to highlight the efficacy of diverse OTC skin, hair, and nail care recommendations for adult cancer patients while encouraging further clinical trials to establish evidence-based management guidelines.


Introduction
Many patients undergoing cancer therapy experience adverse dermatologic events including radiation dermatitis (RD), alopecia, rashes, hyperpigmentation, hand-foot syndrome (HFS), phototoxicity, and nail dystrophy [1,2].These patients often face a multitude of challenges, both physical and emotional, related to the dermatologic effects of their treatments.To help mitigate these issues, patients either independently seek or are encouraged by healthcare providers or peers to follow various skin, hair, and nail care recommendations, many of which are non-evidence based and often restrictive (Table 1).There are frequently no or few citations associated with these recommendations and those that are cited often reference narrative reviews lacking actual evidence from clinical trials.In addition to the questionable validity of these recommendations, the restrictive nature of many can cause undue stress and anxiety for patients.
It is important to investigate the validity of cancer therapy skin, hair, and nail care recommendations to identify and promote evidence-based practices.By prioritizing evidencebased recommendations, clinicians can offer patients interventions that have been rigorously studied and proven effective, promoting their well-being, and optimizing their quality of life throughout their cancer journey.Moreover, evidencebased practices empower clinicians to make informed decisions tailored to individual patient needs.This systematic review aims to summarize current evidence-based recommendations in the literature as they pertain to skin, hair, and nail care management for adult patients before, during, and after cancer therapy, along with a quality of evidence assessment for each supporting study.

Methods
We performed a systematic literature search to identify evidence-based OTC skin, hair, and nail care recommendations for adult patients undergoing cancer treatment.Our systematic review follows the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guidelines [11].Using the PubMed, Cochrane, Embase, and Medline databases, a search for all peer-reviewed articles was performed with the following search terms: "skin care AND chemotherapy," "skin care AND radiation," "skin care AND radiotherapy," "hair care AND chemotherapy," "hair care AND radiation," hair care AND radiotherapy," "nail care AND chemotherapy," "nail care AND radiation, "nail care AND radiotherapy." The abstracts were independently screened using defined criteria for eligibility.Inclusion criteria specified that papers be: written in English and discuss studies of OTC interventions addressing skin, hair, and nail changes in adults age 19 or older receiving chemotherapy or RT for cancer.References from included reports were reviewed and additional sources that were not initially identified were added.Articles were excluded if they were review articles, not available in full text, not in English, animal studies, or studies of pediatric patients, or involved prescription-based therapies (Fig. 1).Animal studies were omitted because they might not accurately reflect human physiology, treatment response, or adverse effects, thereby limiting their relevance to clinical decision-making for humans.Pediatric studies were excluded because skin, hair, and nail care practices are much more common in adults and differ between adults and children.This leads to varying OTC recommendations influenced by differing physiology, treatment protocols, and potential adverse effects, thereby limiting their direct applicability to the targeted adult cancer patient population and their providers in this review.Four reviewers (B.J., L.M.P, S.A.R., and E.T.) independently screened all titles and abstracts.Articles that met inclusion criteria underwent full-text review.In case of disagreement, a consensus meeting was held to resolve discrepancies.Quality of evidence was used to evaluate the strength of a particular recommendation and was assessed and classified by the Oxford Centre for Evidence-Based Medicine 2011 Levels of Evidence (LoE) as previously described [12]: level 1 (systematic review of RCTs or high-quality randomized controlled trial), level 2 (lesser quality RCT or prospective cohort study), level 3 (case-control study, non-randomized controlled cohort or follow-up study), level 4 (case series), or level 5 (expert opinion, mechanism-based reasoning).

Results
The initial database search provided 2301 total articles with 2192 unique articles after removal of duplicates.Seventy-seven articles met inclusion criteria consisting of 54 RCTs, 8 non-randomized controlled cohorts, 1 non-randomized controlled clinical trial, 3 controlled prospective cohorts, 4 prospective cohorts, 2 controlled clinical trials, 1 prospective comparative study, 2 case reports, and 2 case series discussing 9322 patients.An additional article, an RCT of 22 patients, that met inclusion criteria was added from a reference list of a screened article.A total of 78 studies, including 77 articles from the database search and an outside search article, were included in our final review.OTC skin care treatments with the best quality of evidence included moisturizing creams and lotions.Treatments with moderate quality of evidence and efficacy included antimicrobials and antiseptics, dressings, and natural products.Our review revealed a paucity of evidence-based hair and nail care practices.Included articles and results are summarized in Table 2. Avoid: heat exposure (long and hot showers [3], saunas [4]), shaving the armpit with a straight razor [5], application of perfume, deodorant, powder, and lotion in the treatment site [6], application of greasy creams (e.g.pure petroleum), application of topicals prior to RT [7], wearing clothes made of synthetic material [8], wearing tight clothes [4] Recommend: Shower before each treatment with mild unscented soap [5], wash with mild pH, neutral, or non-alkaline soaps [9], free of fragrances, alcohols, fruit, or plant extracts [4] Hair care Avoid: daily shampoo, use of hair clips, barrettes, bobby pins, hair ties, dryers, curling irons, straighteners, hair spray, and dye [10] Recommend: Keep a short hair style [10] Nail care Avoid: manicures and pedicures [3], tight shoes [8], prolonged immersion of hands in water, false nails, and acetone remover [4]

Basic hygiene and routine care
Recommendations pertaining to basic hygiene and routine care exist in other reviews in literature that were not supported by any studies in our systematic review including: avoidance of manicures and pedicures [3], keeping a short hair style, avoiding daily shampoo, avoiding hair manipulation such as using hair clips, dryers, curling irons, dye [10], avoiding shaving the armpit with a straight razor [5], and avoidance of perfume, deodorant, powder, and lotion in the treatment site [6].
We found several evidence-based studies that contraindicate the previous suggestions.In a study, washing the skin with soap and water during the course of treatment was not associated with increased skin toxicity [13].A study evaluating aluminum-based antiperspirant use in women receiving external beam RT for breast cancer found that antiperspirant use was not associated with any significant skin reaction compared to the control group [14].Interestingly, in another study, aluminum-based antiperspirant use in breast cancer patients treated with pegylated liposomal doxorubicin was associated with a decreased incidence of grade 2 or 3 palmar-plantar erythrodysesthesia [15].

Creams, ointments, lotions, and gels
Dermatitis, itchiness, xerosis, and erythema are common side effects of RT but can be ameliorated with the use of creams, ointments, lotions, and/or gels [1,2].Results from a large multi-institutional study found that thin or moderately applied topical agents have minimal effect on RT skin dose [56], negating suggestions that topicals should be avoided prior to RT. Application of topical vitamin E, RayGel, phytotherapic, urea, or antioxidant creams reduced onset and severity of RD [24][25][26]57].Urea-containing creams have shown benefit in preventing HFS during and following chemotherapy [25,26].Analgesic-containing gels, such as trolamine, may also play a role in alleviating acute RD by promoting wound healing.Trolamine use is associated with conflicting results, warranting additional studies of analgesic use for RD [23,58].
Several published studies have found no benefits of certain emollients in acute skin reactions.Hydrosorb and Radiacare gel have been found to be ineffective in treating RD, while Biafine cream has demonstrated mixed results [19][20][21][22].It is important for clinicians to counsel patients  undergoing RT on the use of ineffective creams and gels, which may be found and ordered online.

Dressings
Dressings are often used to treat wounds from RT and since skin toxicity from RT can result in desquamation, many studies have evaluated the utility of dressings in the prevention and treatment of RD.Studies show that Mepitel film, silver nylon dressings, polymeric membrane dressings, 3 M Cavilon No-String Barrier film, Airwall film, Polyurethane hydrofilm, StrataXRT® silicone film, and Mepilex Lite dressing are effective at reducing the duration and frequency of RD [27][28][29][30][31][32][33][34][35].One study found that a wet dressing, Hydrogel, resulted in a significant increase in healing time compared to a dry dressing, Tricotex [36].
While there are currently no standard OTC available treatments in preventing EGFR inhibitor induced acneiform rash, vitamin K has been studied as a possible intervention [60].
Studies have found mixed results with the use of vitamin K cream, with a few studies reporting no reduction in the number of cetuximab induced papulopustular eruptions after use of vitamin K1 and vitamin K3 [44,61].However, there have been a few reports of lower proportions of grade 2 and grade 3 rash after use of vitamin K cream [43,62].Hofheinz et al. found that combination therapy did not decrease grade 2 + skin rash.There is currently no evidence-based recommendation to use vitamin K to prevent EGFR induced skin toxicity [60].

Natural products
Naturally-derived compounds are often incorporated into skincare regimens for their potential anti-inflammatory and antioxidant benefits for RD [39].Three studies in this review evaluated the efficacy of aloe in reducing adverse skin reactions in patients undergoing RT.In two studies, aloe did not significantly reduce RD compared to either placebo or topical aqueous cream [37,38].In another study, adding aloe to a mild soap skin washing regimen demonstrated a protective effect as the cumulative radiation dose increased over time [63].
Other naturally derived compounds that have been investigated in trials include curcumin, Calendula, and Epigallocatechin-3-gallate (EGCG), a bioactive constituent of green tea, all of which demonstrate antioxidant properties [64][65][66].Wolf et al. found that prophylactic treatment with topical curcumin was effective in minimizing skin reactions and pain for patients with high breast separation (i.e., larger breast size) at the end of RT [40].In a RCT comparing topical Calendula cream versus standard of care (Sorbolene), no significant difference was observed for the prevention of RD [41].Zhao et al. investigated whether EGCG can reduce the incidence of RD in patients after breast cancer surgery and found that EGCG prophylaxis significantly reduced both the incidence and severity of RD [42].Cumulatively, these studies suggest that naturally-derived compounds with potential antioxidant properties may confer a protective effect against oxidative stress induced by free radicals during radiation treatment.

Antimicrobials and antiseptics
There are very few studies looking at non-prescription based antimicrobials or antiseptics, such as Gentian violet and chlorhexidine.Gentian violet has shown mixed results in treating RD [16,17].Chlorhexidine did not confer a protective benefit against infections in patients undergoing chemotherapy [18].

Hair care
Scalp cooling (SC) was the most commonly used hair care practice investigated in our review for chemotherapyinduced alopecia.In several trials, SC demonstrated efficacy in preventing chemotherapy-induced hair loss and may work better for patients receiving certain chemotherapies such as anthracyclines [48][49][50][51].Additionally, prolonged post-infusion SC has been associated with better outcomes [52].
A few other studies investigated techniques such as the use of topicals and hair washing practices to prevent hair loss during chemotherapy.A study in patients with alopecia secondary to chemotherapy demonstrated that topical 2% minoxidil significantly reduced the period of baldness [47].A novel topical containing a blend of four botanical ingredients (citrus, cocoa, guarana, and onion) was shown to increase hair density and thickness compared to baseline after 6 months of use [46].Various hair washing techniques have not demonstrated any significant difference in hair loss compared to control [45].Although avoidance of hair dye is a common recommendation, we did not find any articles that referenced hair dye or other chemicals.

Nail care
Nail toxicity has been a well-documented complication of chemotherapy, particularly that of taxane use, causing both functional impairment and psychological distress [67,68].Two studies investigated the use of cryotherapy to prevent docetaxel-induced hand and nail toxicity with conflicting results.While one trial with 41 patients found that onycholysis and skin toxicity were significantly reduced in the frozen glove protected hand [54], another trial with 21 patients found no significant difference between cutaneous hand toxicity in the gloved and non-gloved hands [53].Further studies are needed to investigate whether cryotherapy can be used as an effective intervention to reduce taxane-induced nail and skin toxicity.
Morrison et al. investigated 2 interventions compared to standard of care for taxane-induced nail toxicity in women with early breast cancer [55].Standard of care included lifestyle and hand hygiene practices aimed to prevent nail infection and damage including wearing household gloves when using chemicals, nail filing rather than cutting, and moisturizing hands around the fingernails.Two interventions included nail coverings (painting nails with dark nail varnish thought to prevent UV-induced damage) and Onicolife, a nail-specific medical advice consisting of anti-inflammatory and antiseptic compounds to protect tender and fragile nails).Compared to the use of dark nail varnish, standard care and the specialized Onicolife nail drops and nail oil were significantly associated with less nail toxicity [55].

Discussion
Patients undergoing cancer treatment often experience significant psychological distress and physical discomfort due to changes in their skin, hair, and nails.Unsubstantiated recommendations can add to this distress and hinder patients from resuming their normal lives during and post-cancer therapy, leading to unnecessary stress and anxiety.Clinicians play a pivotal role in assisting patients in maintaining their quality of life and sense of identity throughout the entire cancer treatment process.Therefore, it is imperative for clinicians to identify and counsel patients on evidencebased, effective, safe, and tolerable options for preventing and treating dermatologic disorders associated with cancer treatments.Additionally, it is important to individualize recommendations based on patient values and available evidence.
This systematic review underscores the efficacy of various OTC treatment modalities, with moisturizing creams and lotions having the highest quality of evidence and efficacy.Treatments with moderate quality of evidence and efficacy included antimicrobials and antiseptics, dressings, and natural products.It is important to acknowledge the varying quality of evidence for scalp cooling, a commonly used practice for chemotherapy-induced alopecia, necessitating larger clinical trials for a more comprehensive understanding of its efficacy and safety.Contradictory findings on the use of cryotherapy in taxane-induced nail toxicity as well as nail polishes and nail drops warrant further research in nail care practices.Importantly, recommendations on basic hygiene and routine care, such as avoiding certain practices, lacked support in the systematic review.
The results presented here must be interpreted with caution due to the variability in study sizes and the quality of study design.Certain treatment modalities were characterized by conflicting results and may not be generalizable to all patients.Different studies demonstrate short-term versus long-term benefits, emphasizing the importance of considering the duration of improvement for a given therapy.While the majority of studies in our review involved breast cancer patients, it is important to investigate evidence-based treatments in other cancer types owing to differences in the skin of various body regions.Compared to trials investigating evidence-based skin care regimens, there is a paucity of trials investigating those of hair and nail care.
In this systematic review, we summarized current evidence-based OTC recommendations in the literature as they pertain to skin, hair, and nail care management for adult patients before, during, and after cancer therapy, along with a quality of evidence assessment for each study.We hope that this review serves as a comprehensive guide for clinicians and patients to incorporate evidencebased recommendations and inspires further clinical trials to advance the field of supportive oncodermatology.This approach not only enhances quality of care but also fosters a sense of trust between healthcare providers and patients.

Table 1
Examples of suggested skin, hair, and nail care guidelines

Table 2
Included studies evaluating skin, hair, and nail care treatments in adult patients undergoing cancer therapy